Protein & Cell >

2023 , Vol. 14 >Issue 1: 37 - 50

DOI: https://doi.org/10.1093/procel/pwac027

RESEARCH ARTICLE

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

  • Daming Zuo , 2,9 ,
  • Yu Chen 2 ,
  • Jian-piao Cai 4 ,
  • Hao-Yang Yuan 1 ,
  • Jun-Qi Wu 1 ,
  • Yue Yin 2 ,
  • Jing-Wen Xie 2 ,
  • Jing-Min Lin 2 ,
  • Jia Luo 1 ,
  • Yang Feng 1 ,
  • Long-Jiao Ge 3 ,
  • Jia Zhou 5 ,
  • Ronald J. Quinn 6 ,
  • San-Jun Zhao 7 ,
  • Xing Tong 3 ,
  • Dong-Yan Jin 8 ,
  • Shuofeng Yuan , 4 ,
  • Shao-Xing Dai , 3 ,
  • Min Xu , 1
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  • 1. Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
  • 2. Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China
  • 3. State Key Laboratory of Primate Biomedical Research;Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China
  • 4. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
  • 5. Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
  • 6. Griffith Institute for Drug Discovery, Griffith University, Brisbane 4111, Australia
  • 7. School of Life Sciences, Yunnan Normal University, Kunming 650500, China
  • 8. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
  • 9. Microbiome Medicine Center, Department of Laboratory medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China

Received date: 25 May 2022

Accepted date: 09 Jun 2022

Copyright

2022 The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.
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Abstract

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Key words： hnRNPA2B1; PAC5; HBV; SARS-CoV-2 omicron; TBK1-IRF3 pathway; type I IFNs

Cite this article

Daming Zuo , Yu Chen , Jian-piao Cai , Hao-Yang Yuan , Jun-Qi Wu , Yue Yin , Jing-Wen Xie , Jing-Min Lin , Jia Luo , Yang Feng , Long-Jiao Ge , Jia Zhou , Ronald J. Quinn , San-Jun Zhao , Xing Tong , Dong-Yan Jin , Shuofeng Yuan , Shao-Xing Dai , Min Xu . A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo[J]. Protein & Cell, 2023 , 14(1) : 37 -50 . DOI: 10.1093/procel/pwac027

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